Hey, Bacteria? Can We Talk?

The Princeton microbiologist hopes to make new medicines by listening to the conversations of bacteria.

In her Princeton lab, Bonnie Bassler has identified “chemical words” that bacteria use to work on collective tasks, like launching an infection.

Photo by Frank Veronsky

If bacteria could talk, what would they say? According to Bonnie Bassler, it’s not a matter of if. For more than two decades, the Princeton University microbiologist has listened in on the microbes’ conversations to determine how and why they communicate, what they’re saying to each other, and what they might have to tell us.

It’s fitting to discover that Bassler herself is an eager conversationalist, with a fluid and emphatic delivery that conveys her enthusiasm for science in general and bacteria in particular. That enthusiasm has been repaid with a host of honors, including a MacArthur “genius” fellowship and a nomination by President Barack Obama to the National Science Board. Sitting in her office on the Lower Life-Forms floor of Princeton’s Lewis Thomas Laboratories, she seems delighted to share the story of her subjects and how she came to study them.

It was, she says, “an accident.” Growing up in California, Bassler was passionate about animals. Her parents, non-scientists both, thought she might want to become a veterinarian. That sounded fine to Bassler—until she enrolled at the University of California, Davis and took her first anatomy class. Dissection proved to be more than a stumbling block. “I realized, when we started to cut these animals up,” she says, “that what I love is live animals.”

But while she passed on the idea of becoming a vet, she did like the molecular biology and biochemistry courses that were requirements for veterinary students. One day, while scanning a university bulletin board, she came across a notice seeking students to work in a lab. She was intrigued. “I screwed up my courage to ask this guy if I could be in his lab,” she remembers, “and he put me at a bench and put pipettes in my hand, and I never looked back.” Her initial discovery was her own passion for science. “I realized,” she says, “that I like figuring out how things work.”

She did experience one disappointment. Her boss, Fredrick Troy, was working on two projects, one involving cancer and the other, bacteria. Bassler’s mother had recently died of cancer, and this coincidence got her thinking that she’d found her vocation. “I was like, I will cure cancer; here’s a meaningful life,” she recalls. Except that Troy assigned her to bacterial research. Since she had no say in the matter, she figured she’d work hard, and Troy would move her into cancer research. And then she fell in love with bacteria.

“They reproduced so rapidly that you could have a surprise in the incubator every single day,” she says. She quickly grasped that bacteria weren’t some alien life form, but rather, “simplified models of all the things that we and our cells do.” Bacteria, she says with unabashed affection, “do all these remarkable things, like communicate, engage in group behaviors, kill you, and keep you alive, and make the world work.”

Graduate study at Johns Hopkins served up another epiphany. At a meeting sponsored by the Office of Naval Research, she heard Michael Silverman, a geneticist, talk about V. fischeri, a bioluminescent marine bacterium he was studying. Remarkably, the bacterium lit up only when it found itself in a large group of others of its species—in other words, the bacteria were talking to one another about when they should turn on their lights. Bassler ran to the podium after Silverman’s speech and begged him to take her on as a postdoctoral fellow.

Luckily, he had the good sense to say yes, and in the subsequent years Bassler became one of the preeminent scientists in the field of bacterial communication, or what is now known as quorum sensing (QS). Among her most significant achievements is the revolutionary discovery that bacteria talk not only with members of their own species, but with other bacterial species as well.

Bassler is quick to point out that she didn’t invent the field; that honor, she says, goes to John Woodland “Woody” Hastings, a Harvard biologist who discovered QS in the 1970s, and to Silverman, who applied the tools of genetics to Hastings’s discovery. Which isn’t to downplay Bassler’s contributions. “Bonnie is the world leader in the field of quorum sensing,” says her Princeton colleague and collaborator, Ned Wingreen, a theoretical physicist. “She was responsible more than anyone else for showing that QS wasn’t an oddity, but was universal and hugely important for understanding all bacteria.” In fact, there are literally thousands of species that communicate via QS in order to accomplish tasks that would be unproductive unless a kind of flash mob of bacteria carried them out in synchrony.

Those tasks might be benign—the creation of bioluminescence in oceans, say—or harmful—like making human beings sick. Either way, there’s no doubt that QS allows bacteria to do what they do best. “If one bacterium dribbles out a couple of molecules of a toxin,” notes Bassler, “it doesn’t do anything to you. Your immune system sees a red flag and it hunts the bacterium down.” But if bacteria wait, patiently counting their number until it reaches a critical mass, they can launch an attack that your immune system won’t be able to defeat immediately—or ever.

Of course, bacteria don’t speak the way we understand the term. Instead, they produce specific molecules that Bassler calls chemical words. Thanks to Bassler and her team, we know that the microbial lexicon contains at least three of these words. One is used to communicate among bacteria of the same species, essentially saying, “You’re my identical twin.” Another communicates among all the bacteria in a biological family, sending the message, “You’re my cousin, but you’re not my twin.” A third speaks to bacteria outside the family, stating, “You’re a bacterium, but you’re other.”

As Bassler explains it, “The molecules say how many bacteria are present, so the bacteria are counting. But they’re also distinguishing: Am I with my kin, or am I with someone else?” Depending on their number and what other bacteria are present, they may or may not carry out a collective task, such as launching an infection or forming a so-called biofilm (a community of bacteria) like dental plaque, for example, to adhere to a surface.

At a time when bacteria are increasingly resistant to the medications that fight them, Bassler is hopeful that her work will lead to the development of a new class of antibiotics that would be less likely to meet with resistance. Rather than killing the microbes, these new therapies, using so-called anti-quorum sensing molecules, would jam the receptors for those chemical words through which bacteria communicate. This would render the bacteria incapable of hearing or counting—and therefore, of launching an attack. “They think they’re alone,” Bassler explains.

The development of these new drugs is likely to take at least a decade. But Bassler notes that manipulation of QS could lead to other beneficial applications before then. Anti-QS molecules, for instance, could be used to make infection-resistant medical materials for catheters, intubation devices, joint implants and the like. They could also be used in paints that would keep the hulls of boats clear of barnacles, which can only attach themselves to a surface that is lined with a bacterial biofilm.

Bassler’s enthusiasm serves her well in another of her passions: communicating not just the benefits, but also the joys of science. She has lectured at colleges and universities across the country, and her 2009 TED talk is a YouTube hit.

Don Jay Smith, a coproducer of the New Jersey City University Presidential Speaker Series, at which Bassler was a 2017 presenter, calls her “a role model for young women who aspire to a career in the sciences.” She’s also a one-woman cheering section for scientists.

“Scientists,” says Bassler, “used to be heroes—they were seen as people who devoted their lives to making the world better.” They’re still devoted, she adds, “but somehow, our expertise is less valuable—we’re thought of as dangerous or lunatics.”

Given her ability to communicate her own considerable zeal for the wonders of science, Bassler might just convert the science-resistant among us. “I work on a glow-in-the dark bacterium,” she says, enunciating each word as if she’s still astonished at the fact. “It’s the most beautiful organism in the world, and it does this amazingly cool trick of communicating, and just by studying something that I was curious about, we’re going to make a new medicine for one of the Earth’s most pressing problems.

“Bacteria,” she adds, waxing enthusiastic, “are treasure troves with the potential to do amazing things for humankind.”